Ctsb-flox Mouse

Ctsb, also known as Cathepsin B, is a cysteine protease. It is mainly located in lysosomes and participates in various cellular processes such as protein degradation and antigen processing. It is involved in multiple pathways including the mitochondrial apoptosis pathway, mitophagy-ROS-NLRP3 pathway, and is related to the function of osteoclasts, immune cells infiltration, and autophagy [1-10].

In sepsis-induced acute kidney injury (S-AKI), Ctsb activation via lysosomal membrane permeabilization (LMP) promotes apoptosis through the mitochondrial apoptosis pathway, and its inhibition may be a new treatment strategy [1]. In high-fat-diet-induced hepatic pyroptosis, apigenin alleviates pyroptosis by reducing Ctsb release caused by LMP through the mitophagy-ROS-CTSB-NLRP3 pathway [2]. CST6 protein and peptides can inhibit breast cancer bone metastasis by suppressing Ctsb activity and osteoclastogenesis [3]. In AML, knockdown of Ctsb in HL-60 cells inhibits cell proliferation and tumorigenesis, and may serve as an independent prognostic factor [4]. In gliomas, Ctsb is a negative prognostic biomarker related to immune cells infiltration and immunosuppression [5]. In late middle-aged adults at risk for Alzheimer's disease, aerobic exercise training increases plasma Ctsb, and changes in Ctsb correlate with cognitive performance [6]. In mice, running-induced systemic Ctsb secretion is associated with memory function, and Ctsb knockout mice do not show exercise-enhanced adult hippocampal neurogenesis and spatial memory function [7]. In necroptosis, MLKL polymerization-induced LMP leads to Ctsb release and cell death, and chemical inhibition or knockdown of Ctsb protects cells from necroptosis [8]. Melittin treatment suppresses malignant NSCLC progression through enhancing Ctsb-mediated hyperautophagy [9].

In conclusion, Ctsb is involved in multiple biological processes and diseases. Studies using gene knockout or knockdown models have revealed its role in apoptosis, pyroptosis, cancer metastasis, cell proliferation, cognitive function, and necroptosis. These findings provide insights into potential therapeutic strategies for related diseases.